How Tick-Borne Nairoviruses Evade Human Immune Defenses

Increasing temperatures have expanded tick populations that carry established diseases including Lyme disease and Rocky Mountain spotted fever. Beyond these familiar threats, however, a less well-known family of tick-borne viruses called nairoviruses is emerging. These viruses produce severe fevers and damage organ function when people are bitten by infected ticks. In a recent study published in ACS Infectious Diseases, researchers from University of California Riverside and the United States Military Academy have identified mechanisms by which these viruses hide from the human immune system—knowledge that could enable the development of surveillance systems to track them.

For example, the Crimean-Congo hemorrhagic fever virus represents the global danger that nairoviruses can pose to the public. This viral disease is often fatal and is a threat to people in Africa, the Middle East and Asia. Several newly identified nairoviruses can infect humans, making it critical to understand how these viruses circumvent host immunity and develop countermeasures and biosurveillance tools.

Scientists know that some nairoviruses evade host immunity by producing an enzyme that makes the viruses undetectable. The enzymes remove small proteins—ubiquitin and ISG15 attached to human proteins. Without those proteins, the immune system isn’t alerted to an infection. Researchers wanted to assess whether four species of nairoviruses have enzymes capable of doing this.

The team isolated enzymes from three newly identified orthonairoviruses from patients in Asia and the Pacific Coast tick nairovirus (PCTNV), which has been found in ticks but not in humans. In experiments, the enzymes showed various abilities to remove ubiquitin and ISG15 attached to human proteins. The PCTNV enzyme performed best compared to the three other viral enzymes, suggesting that PCTNV might be able to evade the human immune system better than other nairoviruses. Because this virus is carried by a human-biting tick already known to transmit disease such as Rocky Mountain spotted fever, people along the U.S. West Coast could be at risk for exposure.

The researchers compiled enzyme activity data for ubiquitin from this and other studies, encompassing 13 nairovirus species. They then trained computer models to identify pathogenic nairoviruses, which showed early promise for developing a biosurveillance system.

According to Scott Pegan, corresponding author of the study, “This study reinforces the need to be vigilant about not just tick bites but the type of ticks that an individual has been bitten by as they may carry diseases beyond what we have been used to looking for.” Understanding how nairoviruses skirt host immunity is essential for developing tools to detect and monitor these emerging threats.